Background This study tested the hypothesis that P-31 nuclear magnetic resonance (NMR)-detectable 2-deoxyglucose (2DG) uptake is increased in chronically pressure-overloaded hypertrophied left ventricular myocardium.Methods and Results P-31 NMR spectroscopy was used to determine the transmural distribution of high-energy phosphate levels and 2-deoxyglucose-6-phosphate (2DGP) accumulation during intracoronary infusion of 2DG (15 mu mol . kg body wt(-1). min(-1)) in eight normal dogs and in eight dogs with severe left ventricular hypertrophy (LVH) produced by ascending aortic banding. The ratio of LV weight to body weight was 8.25+/-0.65 g/kg in the LVH group compared with 4.35+/-0.11 g/kg in the normal group (P<.01). Myocardial ATP content was decreased by approximate to 40% and phosphocreatine (PCr) by approximate to 60% in LVH hearts. ATP values were transmurally uniform in LVH and normal hearts, whereas PCr was lower in the subendocardium (Endo) than the subepicardium (Epi) of both groups. The PCr/ATP ratio was lower in LVH hearts (1.72+/-0.05, 1.64+/-0.07, and 1.53+/-0.10 in Epi, midwall, and Endo, respectively) compared with normal hearts (2.36+/-0.05, 2.09+/-0.06, and 1.96+/-0.06; each P<.01 normal versus LVH). Arterial blood levels of glucose, insulin, and free fatty acids were comparable between groups, whereas arterial lactate and norepinephrine levels were significantly higher in the LVH group. 2DG infusion did not affect systemic hemodynamics or myocardial high-energy phosphate or inorganic phosphate levels in either group. At the end of 60 minutes of 2DG infusion, there was no detectable accumulation of 2DGP in the normal hearts. However, seven of the eight LVH hearts showed time-depen dent accumulation of 2DGP, which was linearly related to the severity of hypertrophy (r=.90 for subendocardial 2DGP versus LV weight/body weight). A transmural gradient of 2DGP was present, with greatest accumulation in the subendocardium (3.3+/-1.6, 5.8+/-2.3, and 7.9+/-2.2 mu mol/g in Epi, midwall, and Endo of the LVH hearts, respectively; P<.05 Epi versus Endo).Conclusions The pressure-overloaded hypertrophied left ventricle demonstrated increased accumulation of 2DGP detected with P-31 NMR spectroscopy. Accumulation of 2DGP was positively correlated with the degree of hypertrophy and was most marked in the subendocardium.

With the advent of ultrafast Magnetic Resonance Imaging (MRI), it is now possible to produce images with high temporal resolution. This gives the opportunity to record the passage of the paramagnetic contrast material Gadolinium-DTPA through the tissue of the heart muscle, yielding information on regional myocardial perfusion. We assessed the accuracy of MRI to detect and quantify reductions in coronary flow secondary to stenosis in dogs and patients. Regional blood flow was measured in dogs by left atrial injection of microspheres labeled with different radioactive isotopes. Signal intensity (SI) curves were generated in regions of interest over the myocardium and the cavum of the left ventricle. A newly developed two-compartment model based on the indicator-dilution method was used for interpretation of the SI-curves. In an optimization process the free parameters of the model equation were fitted to the measured SI-curves. The following flow parameters were determined: model parameter Q*, time to peak intensity (T), maximum signal intensity (SImax) and mean transit time (MTT) as calculated from a gamma variate fit. Absolute blood flow values were calculated for the parameters MTT and Q* assuming that the intravascular volume represents 10% of the total myocardial tissue volume. Measurements were performed on a 1.5 T Magnetom SP (Siemens AG, Erlangen) using a Turbo Flash sequence (TR = 6.5 ms, TE = 3 ms, TI = 100 ms, Flip Winkel = 9 degrees). Endsystolic images (voxel size = 1.8, 2.7, 15 mm3) were taken with an 18-cm Helmholtz surface coil in the short-axis view. A Gd-DTPA bolus (0.05 mmol/kg) was injected into the left atrium of 3 anesthetized closed-chest dogs. From the myocardial SI-curves the different parameters of myocardial perfusion were compared with flow assessed by microsphere injection over a wide range of myocardial blood flows (from 0.04 ml/min/g to 7.6 ml/min/g). A third-order polynominal fit showed a good correlation for the parameter Q* and MTT, whereas T and SImax were found to have a poor correlation. The linear regression analysis for a limited range of 2 ml/min/g was significantly underestimated by the MRT-measurements, but the parameter Q* showed the smallest amount of the divergent changes.(ABSTRACT TRUNCATED AT 400 WORDS)

With the advent of ultrafast Magnetic Resonance Imaging (MRI), it is now possible to produce images with high temporal resolution. This gives the opportunity to record the passage of the paramagnetic contrast material Gadolinium-DTPA through the tissue of the heart muscle, yielding information on regional myocardial perfusion. We assessed the accuracy of MRI to detect and quantify reductions in coronary flow secondary to stenosis in dogs and patients. Regional blood flow was measured in dogs by left atrial injection of microspheres labeled with different radioactive isotopes. Signal intensity (SI) curves were generated in regions of interest over the myocardium and the cavum of the left ventricle. A newly developed two-compartment model based on the indicator-dilution method was used for interpretation of the SI-curves. In an optimization process the free parameters of the model equation were fitted to the measured SI-curves. The following flow parameters were determined: model parameter Q*, time to peak intensity (T), maximum signal intensity (SImax) and mean transit time (MTT) as calculated from a gamma variate fit. Absolute blood flow values were calculated for the parameters MTT and Q* assuming that the intravascular volume represents 10% of the total myocardial tissue volume. Measurements were performed on a 1.5 T Magnetom SP (Siemens AG, Erlangen) using a Turbo Flash sequence (TR = 6.5 ms, TE = 3 ms, TI = 100 ms, Flip Winkel = 9 degrees). Endsystolic images (voxel size = 1.8, 2.7, 15 mm3) were taken with an 18-cm Helmholtz surface coil in the short-axis view. A Gd-DTPA bolus (0.05 mmol/kg) was injected into the left atrium of 3 anesthetized closed-chest dogs. From the myocardial SI-curves the different parameters of myocardial perfusion were compared with flow assessed by microsphere injection over a wide range of myocardial blood flows (from 0.04 ml/min/g to 7.6 ml/min/g). A third-order polynominal fit showed a good correlation for the parameter Q* and MTT, whereas T and SImax were found to have a poor correlation. The linear regression analysis for a limited range of < 2 ml/min/g showed a superior estimation of myocardial perfusion for the parameter Q* than MTT. Blood flow > 2 ml/min/g was significantly underestimated by the MRT-measurements, but the parameter Q* showed the smallest amount of the divergent changes.(ABSTRACT TRUNCATED AT 400 WORDS)

With the advent of ultrafast Magnetic Resonance Imaging (MRI), it is now possible to produce images with high temporal resolution. This gives the opportunity to record the passage of the paramagnetic contrast material Gadolinium-DTPA through the tissue of the heart muscle, yielding information on regional myocardial perfusion. We assessed the accuracy of MRI to detect and quantify reductions in coronary flow secondary to stenosis in dogs and patients. Regional blood flow was measured in dogs by left atrial injection of microspheres labeled with different radioactive isotopes. Signal intensity (SI) curves were generated in regions of interest over the myocardium and the cavum of the left ventricle. A newly developed two-compartment model based on the indicator-dilution method was used for interpretation of the SI-curves. In an optimization process the free parameters of the model equation were fitted to the measured SI-curves. The following flow parameters were determined: model parameter Q*, time to peak intensity (T), maximum signal intensity (SImax) and mean transit time (MPT) as calculated from a gamma variate fit. Absolute blood flow values were calculated for the parameters MTT and Q* assuming that the intravascular volume represents 10 % of the total myocardial tissue volume. Measurements were performed on a 1.5 T Magnetom SP (Siemens AG, Erlangen) using a Turbo Flash sequence (TR = 6.5 ms, TE = 3 ms, TI = 100 ms, Flip Winkel = 9 degrees). Endsystolic images (voxel size = 1.8, 2.7, 15 mm(3)) were taken with an 18-cm Helmholtz surface coil in the short-axis view. A Gd-DTPA bolus (0.05 mmol/kg) was injected into the left atrium of 3 anesthetized closed-chest dogs. From the myocardial SI-curves the different parameters of myocardial perfusion were compared with flow assessed by microsphere injection over a wide range of myocardial blood flows (from 0.04 ml/min/g to 7.6 ml/min/g). A third-order polynominal fit showed a good correlation for the parameter Q* and MTT, whereas T and SImax were found to have a poor correlation. The linear regression analysis for a limited range of < 2 ml/min/g showed a superior estimation of myocardial perfusion for the parameter Q* than MTT. Blood flow > 2 ml/min/g was significantly underestimated by the MRT-measurements, but the parameter Q* showed the smallest amount of the divergent changes. In our study of 10 healthy human subjects and 10 patients the Gd-DTPA bolus was delivered through an intravenous catheter placed in the right subclavian vein. Patients with a significant proximal coronary artery stenosis identified by selective coronary angiography were found to have significantly lower blood flow values in regional myocardium with wall motion impairment compared to the non-diseased myocardium. It is concluded that ultrafast MRI can measure myocardial blood flow over a limited but clinically relevant range of flows as defined as slightly above normal to ischemic.

The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180 degrees inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T1-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI.

By administering gadolinium-diethylenetriamine-penta-acetic acid (Gd-DTPA) in conjunction with the Turbo-Flash sequence, the authors assessed the potential of dynamic contrast-enhanced ultrafast magnetic resonance imaging (MRI) to detect and quantify reductions in myocardial perfusion secondary to stenosis and hyperemia induced by Dipyridamole. In ten subjects and three dogs signal intensity-time curves were generated in regions of interest over myocardium. A one-compartment model was introduced to describe the kinetics of Gd-DTPA. The first results indicate that measurements of Gd-DPTA kinetics seem of potential value for the non-invasive assessment of myocardial perfusion